Investigations in this laboratory have recently identified and mapped four discrete loci of intracardiac ganglion cells in the rat. The objective of the proposed research is to determine whether individual populations of cardiac vagal preganglionic neurons (nucleus ambiguus or dorsal motor nucleus) differentially innervate the intracardiac ganglion cells and provide differential control of regional parasympathetic nerve activity and cardiac function. The specific aims are: 1) to determine the anatomical organization of the terminal projections of cardiac vagal preganglionic neurons, and 2) to test the hypothesis that individual populations of parasympathetic preganglionic neurons can cause specific regional changes in: a) intracardiac ganglion cell activity, b) cardiac parasympathetic nerve activity, and c) cardiac function. The neural pathways between preganglionic cell bodies and the heart will be traced by anterograde and retrograde tracer techniques. Existing literature is consistent with the hypothesis that some preganglionic neurons terminate in ventricular regions void of ganglion cells; the proposed studies will use retrograde tracers to investigate this question. It is proposed to investigate the influence of stimulation of different populations of cardiac vagal preganglionic neurons on: a) the intracardiac ganglion cells, by accumulation of radiolabeled 2-deoxyglucose in the ganglion cells, b) regional cardiac parasympathetic nerve activity, by measuring regional acetylcholine turnover, and c) indices of cardiac function - heart rate, atrio-ventricular nodal conduction, and cardiac contractility. It is anticipated that stimulation of individual populations of preganglionic neurons will differentially activate specific loci of ganglion cells which shall be reflected in selective changes in parasympathetic nerve activity and cardiac function. Alterations in parasympathetic control of the heart occur in various pathological states for which there are animal models, such as diabetic neuropathy and cardiomyopathy. Abnormalities of specific populations of neurons, or changes in the differential innervation of the intracardiac ganglion cells, may be contributing factors in the development of the disease. Identification of the relationships between the vagal preganglionic neurons, the intracardiac ganglion cells, and the effector sites in normal animals is fundamental to future investigations of cardiac autonomic dysfunction.